Allogeneic Hematopoietic Stem Cell Transplantation for Myeloma: Time for an Obituary or Not Just Yet!

The management of myeloma has evolved dramatically in the last two decades. High dose melphalan and autologous hematopoietic stem cell transplantation (HSCT) marked the beginning of this journey. This was followed by an explosion of novel agents which were approved for management of myeloma. Allogeneic HSCT which was deemed as the only curative option was largely abhorred due to high transplant-related mortality (TRM) until the advent of reduced intensity conditioning (RIC). An approach of tandem autologous and RIC-allogeneic transplantations has showed the best promise for cure for this condition, particularly for those with high-risk cytogenetics. Yet, allogeneic HSCT seems to have fallen out of favor due to the projected high TRM and late relapses, even though the alternatives do not offer a cure, but merely prolong survival. Offering an allogeneic HSCT as a final resort in unlikely to yield gratifying results. At the same time, allogeneic HSCT needs to evolve in a disease-specific manner to address the relevant concerns regarding TRM and relapse. With the introduction of effective GVHD prophylaxis in the form of post-transplantation cyclophosphamide, transplantation from a haploidentical family donor has become a reality. The challenge lies in segregating graft-vs-myeloma effect from a graft-versus-host effect. We discuss the pro-survival and anti-apoptotic pathways via CD28-CD86 interactions which confer survival advantages to myeloma cells and the possibility of disruption of this pathway in the context of haploidentical transplantation through the use of CTLA4Ig without incurring T cell alloreactivity.